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Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes

Petrović, Voin and Petrović, Sandra and Joksi, Gordana and Savić, Jasmina and Čolović, Mirjana and Cinellu, Maria Agostina and Massai, Laura and Messori, Luigi and Vasić, Vesna (2014) Inhibition of Na+/K+-ATPase and cytotoxicity of a few selected gold(III) complexes. Journal of Inorganic Biochemistry, Vol. 140 , p. 228-235. ISSN 0162-0134. eISSN 1873-3344. Article.

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DOI: 10.1016/j.jinorgbio.2014.07.015

Abstract

Na+/K+-ATPase is in charge of maintaining the ionic and osmotic intracellular balance by using ATP as an energy source to drive excess Na+ ions out of the cell in exchange for K+ ions. We explored whether three representative cytotoxic gold(III) compounds might interfere with Na+/K+-ATPase and cause its inhibition at pharmacologically relevant concentrations. The tested complexes were [Au(bipy)(OH)2][PF6] (bipy = 2,2′-bipyridine), [Au(pydmb-H)(CH3COO)2] (pydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-pyridine), and [Au(bipydmb-H)(OH)][PF6] (bipydmb-H = deprotonated 6-(1,1-dimethylbenzyl)-2,2′-bipyridine). We found that all of them caused a pronounced and similar inhibition of Na+/K+-ATPase activity. Inhibition was found to be non-competitive and reversible. Remarkably, treatment with cysteine resulted in reversal or prevention of Na+/K+-ATPase inhibition. It is very likely that the described effects may contribute to the overall cytotoxic profile of these gold complexes.

Item Type:Article
ID Code:10673
Status:Published
Refereed:Yes
Uncontrolled Keywords:Sodium pump, Gold(III) complexes, human blood cells, inhibition, cytotoxicity
Subjects:Area 03 - Scienze chimiche > CHIM/03 Chimica generale e inorganica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Chimica e Farmacia
Publisher:Elsevier
ISSN:0162-0134
eISSN:1873-3344
Deposited On:22 Jan 2015 11:52

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